Macrophage‐derived cytokine and nuclear factor κB p65 expression in synovial membrane and skin of patients with psoriatic arthritis

CL Danning, GG Illei, C Hitchon… - … : Official Journal of …, 2000 - Wiley Online Library
CL Danning, GG Illei, C Hitchon, MR Greer, DT Boumpas, IB McInnes
Arthritis & Rheumatism: Official Journal of the American College …, 2000Wiley Online Library
Objective Monocyte‐derived cytokines are important mediators in synovitis and represent
novel therapeutic targets. This study was undertaken to analyze their expression in synovial
membrane (SM) of patients with psoriatic arthritis (PsA) compared with that in skin of patients
with PsA and SM of patients with rheumatoid arthritis (RA). Methods Multiple synovial biopsy
samples (24 from patients with PsA, 20 from patients with RA, 5 from patients with
osteoarthritis [OA]) and skin biopsy samples (lesional and perilesional skin from 25 PsA …
Objective
Monocyte‐derived cytokines are important mediators in synovitis and represent novel therapeutic targets. This study was undertaken to analyze their expression in synovial membrane (SM) of patients with psoriatic arthritis (PsA) compared with that in skin of patients with PsA and SM of patients with rheumatoid arthritis (RA).
Methods
Multiple synovial biopsy samples (24 from patients with PsA, 20 from patients with RA, 5 from patients with osteoarthritis [OA]) and skin biopsy samples (lesional and perilesional skin from 25 PsA patients) were obtained. Standard leukocyte antigens, cytokines (tumor necrosis factor α [TNFα], interleukin‐1α [IL‐1α], IL‐1β, IL‐15, and IL‐10) and the transcription factor nuclear factor κB (NF‐κB; active p65 subunit) were localized and quantified immunohistochemically by light microscopy and digital image analysis.
Results
Sublining cellular infiltration, lymphoid aggregation, and vascularity were similar in PsA and RA SM. Lining layer thickness was greater in RA SM, associated with more CD68+ macrophages. In PsA SM, TNFα, IL‐1α, IL‐1β, IL‐15, and IL‐10 were primarily localized to lining layer and perivascular macrophages, as were cells expressing the active subunit of NF‐κB (p65). TNFα, IL‐1β, and IL‐15 expression in PsA lining layer was less than that in RA lining layer, likely reflecting lower macrophage numbers. In sublining areas, levels of TNFα and IL‐15 were lower in PsA patients than in RA patients, whereas IL‐1α and IL‐1β expression was equivalent. IL‐10 was identified at similar levels in RA and PsA SM lining layer and sublining. Expression of NF‐κB (p65) was equal in lining layer from both patient groups, but lower in PsA than RA sublining. Histologic findings did not correlate with clinical parameters of disease. Cytokine expression in skin did not correlate directly with that in SM. Cytokine expression was greater in PsA and RA SM than in OA SM.
Conclusion
This study shows, for the first time, that monocyte‐derived cytokines are found in PsA SM and demonstrates the relative paucity of the antiinflammatory cytokine IL‐10 in PsA skin and SM. Significant divergence from RA SM expression was observed, despite similar clinical and demographic features in the 2 patient groups.
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